Our aim is to understand the structure-function relationship of tRNA molecules by studying the role of the modified nucleosides in tRNA. Our objective is to establish, by x-ray diffraction techniques, the details of the stereochemistry of the modified bases, nucleosides and nucleotides in the monomeric and polymeric states and establish any conformational restrictions they impose on the polynucleotide chain of tRNA. We will develop and evaluate proposals for the role of modified nucleosides in tRNA, particularly the hypermodified bases adjacent to the anticodons in tRNA. We will investigate the details of the stereochemistry of codon- anticodon interactions. We shall study cytokinins that bear a strong resemblance to the hypermodified bases and investigate the mechanism of action of cytokinins. We shall study stereochemical criteria that will be of some help in developing a rational chemotherapy program involving modified bases, their analogs and derivatives.